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Biomedical subjects

M G Bernengo

Publications and source records attributed to M G Bernengo.

At least 55 records · Page 3Linked to original sources
PubMed1993

Therapy for metastatic melanoma: effective combination of dacarbazine, carmustine, cisplatin and tamoxifen.

Thirty-two patients with metastatic melanoma received combination chemotherapy and hormonal therapy. Treatment included Carmustine, Cisplatin, Dacarbazine and Tamoxifen (BCDT). The overall response rate was 47%: five patients had a complete response (16%), 10 patients had a partial response (31%) and two had no response (6%). The median survival for responders was 10 months (range 2-20). The BCDT regimen was equally effective against soft tissue and visceral metastases. Neither survival or response rate was modified by pretreatment with alpha-interferon (alpha-IFN). In agreement with the results of a recent randomized trial comparing the efficacy of Dacarbazine with that of Dacarbazine plus Tamoxifen, a better survival was found in women than in men: although the response rate was identical (47%), the median duration of response was higher for women. A fall in serum soluble IL-2 receptor (sIL-2R) levels after therapy was seen in responding patients, confirming the usefulness of this parameter in monitoring disease evolution.

Adult↗
PubMed1992

Thymopentin in Sézary syndrome.

BACKGROUND: Response to the treatment of Sézary syndrome (a cutaneous T-cell lymphoma) is poor. Since patients with this syndrome are elderly, aggressive chemotherapy is poorly tolerated and deep immunodepression may result in fatal opportunistic infections. Immunomodulating therapy seems important in the management of Sézary syndrome. PURPOSE: In a pilot study, we assessed the efficacy of thymopentin (TP-5), a synthetic pentapeptide, correlating clinical responses to the histologic and immunologic effects of the drug. METHODS: Twenty Sézary syndrome patients received 50 mg TP-5 intravenously three times a week for a mean time of 16.3 months. Skin and lymph node histology and immunohistochemistry, circulating lymphoid cell subpopulations, and soluble interleukin-2 receptors were evaluated before treatment and during follow-up. RESULTS: Eight complete remissions and seven partial remissions were obtained (75%). No change was observed in three patients, and disease progression was observed in two patients. The median duration of response was 22 months (complete remission, 25.5 months; partial remission, 14 months). Four-year survival probability was 53.9%. The responses were obtained when circulating Sézary cells were less than 2600/mm3. A significant reduction of CD4+ cells paralleled a CD8+ cell increase. An increase in NK cells (CD16+ and CD56+) was accompanied by significantly longer survival. Serum soluble interleukin-2 receptor values were a useful monitor of the clinical course and treatment. Loss of epidermotropism, reduction of Langherhans' cells, and HLA-DR+ keratinocytes were found. CONCLUSIONS: TP-5 is a potentially useful agent in the treatment of a subgroup of patients with Sézary syndrome; its activity seems to be mediated by an effect on a normal NK cell-like subpopulation. IMPLICATIONS: The biological and clinical role of this therapy in combination with conventional treatments will be the subject of future investigations.

Aged↗
PubMed1992

Expression and role of integrin receptors in Sézary syndrome.

The potential role of integrins in the epidermotropism of the atypical lymphocytes of Sézary syndrome was studied by monitoring the expression of alpha and beta chains and their major ligands in skin biopsies and peripheral blood cells in patients at different progression stages. Most mononuclear cell integrins were also detected on infiltrating cells including the leukocyte complex CD11/CD18, alpha 4 beta 1, and their ligands, ICAM-1 and VCAM-1. Conversely, alpha 6 and beta 4 were present only in epidermal basal cells. Mononuclear infiltrates of SS were positive for both alpha 3 and alpha 5 chains, whereas in inflammatory cutaneous diseases only alpha 5 was expressed, indicating that a major feature of Sézary cells is the unique expression of alpha 3 beta 1. Significant changes of alpha 3 beta 1 were monitored in the follow-up of Sézary patients and correlated with the results of the therapy. The heterodimer alpha 1 beta 1 was absent from mononuclear cells except in one case. Among matrix molecules, laminin and type IV collagen displayed a pattern similar to that of the controls, whereas fibronectin and tenascin deposition were apparently increased. Circulating Sézary cells, both at diagnosis and during follow-up, were alpha 3 and alpha 5 negative and failed to acquire these adhesion molecules after mitogenic stimulation. We propose that the expression of alpha 3 beta 1 is a distinguishing feature of skin-infiltrating Sézary cells and may be related to their epidermotropism. It could also be adopted as an additional parameter of the progression and therapeutic stage of Sézary syndrome.

Antigens, CD↗
PubMed1992

Soluble interleukin-2 receptor, CD4 and CD8 levels in melanoma: a longitudinal study.

Serum levels of soluble(s) interleukin-2 receptor (IL-2R), sCD4 and SCD8 were analysed in 227 melanoma patients, using a sandwich enzyme immunoassay. Different stages of the disease were considered, and a longitudinal study with a 2-year follow-up was performed. Mean values of sIL-2R were significantly higher than in normal controls in all stages and correlated with the disease progression. sCD8 increases with stage progression were less striking, while sCD4 values were always in the normal range. We conclude that sIL-2R measurement is a useful clinical parameter in monitoring disease evolution in melanoma.

Adult↗
PubMed1992

BANS: a discussion of the problem.

The significance of the BANS location (upper Back, posterior Arm, Neck and Scalp) as a prognostic factor in patients with stage I melanoma is controversial. A meta-analysis performed by Weinstock et al. on their own and five comparable studies corroborated the hypothesis that this location is influential in the prognosis of intermediate thickness (0.76-1.69 mm) melanomas. Our study investigated the relationship between BANS subsites, thickness and prognosis in 1,082 stage I melanoma patients from two major Italian centres, Turin and Florence. A BANS primary was observed in 212 (19.5%) patients: recurrences occurred in 85 of them (40.1%) vs 309/870 non-BANS patients (35.5%). Overall survival probabilities were significantly shorter (p less than 0.01) in the BANS group (69.1% vs 76.7% at 5 years; 59% vs 68.5% at 10 years). The prognostic value of the BANS location was confirmed by a multivariate analysis using the Cox proportional hazards model. Stratification of BANS and non-BANS groups by thickness clusters showed a significant difference in both survival (p less than 0.001) and disease-free interval (p less than 0.05) in the 3.01-4.00 mm thickness subset, due to the greater incidence of distant and visceral metastases. In the 0.76-1.69 mm thickness range the significance was p = 0.06.

Adolescent↗
PubMed1991

What is the role of sensitization in uremic pruritus? An allergologic study.

Patch tests were carried out to evaluate the presence of a sensitization to some components of dialytic circuits in 17 uremic patients complaining of pruritus of unknown origin. Fragments of different dialyzer membranes, of tubing sets, of dialyzer membranes recently resterilized with ethylene oxide and the International Contact Dermatitis Research Group standard series substances were tested. Neither patients nor healthy subjects reacted positively to patch tests, which leads us to question the role of contact allergy in the determination of uremic pruritus.

Adult↗
PubMed1990

Phase II study of interferon alpha-2a and dacarbazine in advanced melanoma.

Based on the report of some activity of combination therapy with dacarbazine (DTIC) and interferon alpha-2a (rIFN alpha-2a) in disseminated melanoma, we conducted a phase II study to determine the feasibility and efficacy in a large series of patients. DTIC was administered in 79 patients at the dose of 800 mg/m2 every 3 weeks and rIFN alpha-2a was given daily at the dose of 9 X 10(6) IU for the first 10 weeks and three times a week thereafter. Among the 75 evaluable patients, 25% achieved an objective response, with 8% complete and 17% partial remissions. The regression occurred within a mean time of 1.9 +/- 1.03 months from starting therapy and the mean duration of response was 8.2 +/- 4.2 months. The major side effects were vomiting, anorexia, fever, fatigue, and myalgia. There was one death related to sepsis after myelosuppression. In the other patients bone marrow and liver toxicities were not remarkable. Our data reveal that a combination regimen of rIFN alpha-2a with a cytotoxic agent has some therapeutic activity in the management of advanced malignant melanoma.

Adolescent↗
PubMed1990

Ki67 antigen expression correlates with tumor progression and HLA-DR antigen expression in melanocytic lesions.

Advanced steps of tumor progression are generally characterized by an increased growth fraction within the neoplastic cell population. The presence of a relevant growth fraction is also related to widely accepted prognostic parameters in some human malignancies. Our aims were to evaluate the presence of a growth fraction with Ki67 monoclonal antibody (MoAb), and to correlate it with tumor progression and HLA-DR antigen expression in 88 melanocytic lesions. The lesions were 19 acquired melanocytic nevi, 58 primary melanomas [divided into 26 superficial spreading melanomas (SSM), 24 superficial spreading melanomas with nodular areas (SS + NM), and five nodular melanomas (NM)], and 11 metastases from malignant melanomas. Ki67 MoAb stained 16%, 19%, 71%, 100%, and 82% of nevi, SSM, SS + NM, NM, and metastases, respectively. Among primary melanomas, Ki67 MoAb stained 12%, 28%, 50%, and 70% of tumors less than 0.75, 0.75-1.49, 1.5-2.9, and greater than or equal to 3 mm thick, respectively. A concordant reactivity pattern for Ki67 and HLA-DR antigens was found in 72% of lesions (p less than 0.0001). We have shown that a representative growth fraction (ie, Ki67 reactivity) is present in melanocytic lesions only in advanced steps of tumor progression and correlates with HLA-DR antigen expression. Despite the different biologic values of Ki67 and HLA-DR antigens, we suggest the joint evaluation of both antigens as a useful marker of aggressive behavior in melanoma.

Antibodies, Monoclonal↗
PubMed1990

[Serum levels of soluble receptors of interleukin-2 in skin pathology].

The antigenic activation of T lymphocytes depends on the production of interleukin-2 (IL-2) and on the expression of a membrane-specific receptor (IL-2R). This receptor, a dimer composed of a 57 kD chain, is also present on some B lymphocytes and activated macrophages (anti-TAC) grouped together in CD25. A soluble form of IL-2R (sIL-2R) was recently identified, comprising the extracellular part of the chain (45 kD) which is released by the cell in body fluids. The presence of sIL-2R in serum can be assayed using ELISA (Cell free, T cell Sciences, Cambridge, MA). Normal values range between 100 and 500 U/ml, with a mean value of 375 U/ml. Marked increases of sIL-2R, with levels of up to 50,000 U/ml, have been observed in various diseases: hairy cell leukemia, Hodgkin's disease, non-Hodgkin lymphoma, acute leukemia, B-CLL, ATL and Sezary's syndrome. Lesser increases are also found in autoimmune diseases, viral infections, and following organ transplantation. Many Authors have described the close correlation between sIL-2R levels and the clinical evolution of the disease. Soluble IL-2 receptors were studied in 184 patients affected by skin diseases: eczematous dermatitis, lichen, psoriasis, erythroderma psoriaticum, dermatomyositis, scleroderma bullous dermatosis, melanoma, Kaposi's disease, lymphomatoid papulosis, non-Hodgkin lymphoma, mycosis fungoides (MF), Sezary's syndrome (SS). Increased serum levels of sIL-R2 were found in non-neoplastic dermatological diseases, including autoimmune related pathologies. Values were normal (396 +/- 170 U/ml) in patients affected by Stage 1 melanoma, but increased (558 +/- 291 U/ml) in cases with visceral involvement.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1989

Phase II trial of recombinant alpha-2b interferon in the treatment of metastatic skin melanoma.

A pilot study was undertaken to evaluate toxicity and activity of recombinant alpha-2b interferon in patients with metastatic malignant melanoma. Interferon was administered at the dosage of 10 x 10(6) IU/m2, 3 times a week i.m. 21 patients entered the study, 17 pretreated with chemotherapy and/or immunotherapy and 6 untreated. We obtained 3 partial responses (14.3%; 95% CL, 3.0-36.3%); 9 patients had stable disease. All patients experienced flue-like symptoms and fever; most fatigue and worsening of performance status. Recombinant interferon alpha-2b at the dosage and schedule used has limited but definite activity in metastatic malignant melanoma; the substantial subjective toxicity must be taken into consideration. Further trials testing recombinant alpha interferon in combination with chemotherapeutic agents, like DTIC, are warranted.

Adult↗
PubMed1988

Immunomodulation and Sézary syndrome: experience with thymopentin (TP-5).

The clinical, histological and immunological effects of long-term treatment with thymopentin (TP-5), administered 50 mg i.v. three times a week on alternate days, in four patients with Sézary syndrome is reported. In all four cases reduction of itching, oedema, scaling and thickening, and clearing of erythroderma were noted after 2 months treatment. Peripheral blood Sézary cells decreased in three cases. Reduction or suspension of the drug was followed by a clinical relapse. A loss of epidermotropism and a reduction in cell infiltrates were observed together with a dramatic reduction in epidermal and dermal Langerhans cells. An increase in the proliferative response to mitogens and in IFN-gamma production, and the expression of activation antigens in PHA stimulated cultures occurred after 3 months. HNK-I+ cells increased both in the peripheral blood and in the dermis following a transient increase in IL-2 receptors, suggesting that clinical response in TP-5 treated patients may be mediated by an increased production of IL-2 and consequent generation of cytotoxic cells or release of lymphokines able to augment NK activity.

Adjuvants, Immunologic↗